Immunoglobulins are administered to patients for the treatment of a number of infectious and immuno-regulatory disease states. The care of the patient is possible through intravenous administration with a sufficient amount of immunoglobulin. Thereby, the use of preparations with a maximal concentration of 5% or 6% is common. However, with respect to the high reliability of the infusion, highly concentrated preparations are desirable. The infusion time could be substantially shortened by the use of smaller volumes.
R. I. Schiff et al., J. Allergy Clin. Immunol., 88, 1991, 61-67, describes a lyophilised preparation which was reconstituted to a 3, 6, 9 and 12% solution. It was found that the osmolarity of the solution was very high. For example, a 12% solution had an osmolarity of 1074 mOs/l. Simultaneously, it was observed that the viscosity of the preparation was also very high. A 12% solution could hardly be administered to children in a reasonable time without difficulties. It was stated that concentrations of more than 12% are too viscous for routine use.
The osmolarity of an isotonic solution, i.e. a solution possessing the same osmotic pressure as human blood, amounts to about 300 mOs/l. In order to guarantee a good tolerance of an intravenously administrable preparation, it is desirable therefore that this has an osmolarity of less than 1000 mOs/l, and, ideally, an value corresponding to isotonicity.
Furthermore, the occurrence of IgG aggregates must be prevented in the intravenously tolerable immunoglobulin preparations. These aggregates lead namely to an undesirable anti-complimentary activity and therewith are associated with a number of side effects. Therefore, attention is paid in the formulation of a preparation that it is produced by a process which includes the removal of aggregates of this type and/or the prevention of aggregate formation. After formulation of the preparation, it is preserved preferentially through lyophilisation. However, A. M. Herrera et al., J. Allergy Clin. Immunol., 84, 1989, 556-561, suspected that aggregate formation results again through the lyophilisation of the immunoglobulin preparations.